Oral antidiabetics are the drugs used to control blood sugar in diabetic subjects. The greatest risk of using these drugs is hypoglycaemia, which can be fatal if managed inappropriately. The diagnosis of hypoglycemia may be simple in diabetic subjects but can become a challenge in subjects with no history of exposure to these drugs. The major interest of testing for these compounds in hair is in the case of unexpected hypoglycaemias, as it enables discrimination between hypoglycaemias caused by antidiabetics and other reasons (e.g. insulinoma). Therefore it is important for a toxicology laboratory to screen for antidiabetics in hair due to the large window of detection this matrix allows associated to its long stability over time.

In this study, a method has been developed and validated using liquid-chromatography coupled to tandem mass spectrometry for the analysis of 13 oral antidiabetics in hair.

After addition of three different internal standards (hydroxy-tolbutamide-d9 for sulfonylureas, repaglinide-ethyl-d5 for glinides and vildagliptin-d3 for gliptins) and incubation in an ultrasonic bath in methanol, the hair was dissolved in NaOH and then subjected to liquid–liquid extraction. The validation procedure demonstrated an acceptable linearity for all compounds between 1 and 50,000 pg/mg. LOD and LOQ were between 0.5 and 5 pg/mg and 1–10 pg/mg respectively. Repeatability and reproducibility were below 20 % at two concentrations for all the analytes. The method was successfully applied to the hair of 18 diabetic patients under treatment of oral antidiabetics. The hair tested positive for gliclazide (3–21,400 pg/mg), sitagliptin (1.4–1.8 pg/mg), vildagliptin (3.3 – 1,740 pg/mg) and repaglinide (14.1 pg/mg).

口服降糖药是用于控制糖尿病患者血糖的药物。使用这些药物的最大风险是低血糖，如果管理不当可能会致命。糖尿病受试者的低血糖诊断可能很简单，但对于没有接触这些药物史的受试者来说可能是一个挑战。测试头发中这些化合物的主要目的是在意外低血糖的情况下，因为它能够区分由抗糖尿病药和其他原因（例如胰岛素瘤）引起的低血糖。因此，对于毒理学实验室来说，筛选头发中的抗糖尿病药物非常重要，因为这种基质具有较大的检测窗口，这与它的长期稳定性有关。

在这项研究中，开发并验证了一种使用液相色谱法与串联质谱法相结合的方法，用于分析头发中的 13 种口服降糖药。

加入三种不同的内标（磺酰脲类的羟基甲苯磺丁脲-d9、格列奈类的瑞格列奈-乙基-d5和格列汀类的维格列汀-d3）并在甲醇中的超声波浴中孵育后，将头发溶解在NaOH中，然后进行液体处理——液体萃取。验证程序证明了所有化合物在 1 到 50,000 pg/mg 之间的可接受的线性。LOD 和 LOQ 分别在 0.5 和 5 pg/mg 和 1-10 pg/mg 之间。所有分析物在两种浓度下的重复性和重现性均低于 20%。该方法成功应用于18例口服降糖药治疗的糖尿病患者的头发。头发检测出格列齐特（3–21,400 pg/mg）、西格列汀（1.4–1.8 pg/mg）、维格列汀（3.3–1,740 pg/mg）和瑞格列奈（14.1 pg/mg）呈阳性。